Osteoarthrosis (OA) is an extremely common disorder, especially in the elderly. Despite extensive investigation, the pathogenetic mechanisms responsible for OA have not been well defined. In part, this has been due to the unavailability of suitable tissue exhibiting early changes of OA for study. It is proposed in this investigation to utilize a group of naturally occurring models for OA, the chondrodystrophies. This is a group of rare inherited disorders of cartilage characterized by disproportionate dwarfism and a strong predispostion to OA. Iliac crest cartilage from these patients will be studied in detail since it is potentially available and because there are a number of reasons to think that information gained from the study of this cartilage will be applicable to articular cartilage and OA. When available, articular cartilage from such patients will also be investigated. Articular cartilage from patients with typical OA will be examined for comparison and correlation with the dystrophic cartilage. In all instances, the cartilage proliferation and maturation process will be carefully assessed. This physiologic process appears to be common to both normal endochondral ossification and the repair of damaged articular cartilage; it may be defective in both the chondrodystrophies and in OA. Since abnormalities in the major constituents of cartilage have been implicated in the pathogenesis of both OA and the chondrodystrophies, the major focus of this investigation will be to search for specific abnormalities in these substances. A combination of histochemical, immunohistochemical, lectin histochemical, electron microscopic, and microchemical methods will be used to determine if abnormalities exist in the distribution and content of types I, II and III collagen, proteoglycan core rotein, glycosaminoglycan, fibronectin, glycogen, lipid, calcium, lysozyme, cathepsin, factor VIII, and alkaline and acid phosphatase activity. It is expected that specific abnormalities will be found in both instances thus establishing these disorders as models for OA, and furthermore that new insights into the pathogenesis of OA will be gained.